Skin penetration by the cercarial stage of the human trematode parasite Schistosoma mansoni is mediated by the secretion of proteolytic enzymes able to digest components of mammalian connective tissues. In the present study the purification of these proteinases from cercarial homogenates is reported. The major proteinase species has a mol. wt. of approx. 25 000 and exists in monomeric form as determined by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. This proteinase has an isoelectric point of 6.0. Studies presented here, with a variety of substrates and inhibitors, confirm previous claims that these proteinases belong to the serine class, and, in addition, suggest that they resemble the vertebrate chymotrypsins rather than trypsins or elastases. However, the amino acid composition of the cercarial proteinase differs significantly from bovine chymotrypsin and from the human leucocyte chymotrypsin-like cathepsin G. The amino-acid-composition differences between these proteinases are consistent with their differences in isoelectric point. In order to obtain an insight into the role of the proteinase in skin penetration, its activity on cartilage proteoglycan monomers and on the isolated peptide backbone of proteoglycan was studied. The results of the present study indicate that the cercarial enzyme catalyses a limited specific digestion of the peptide core.
Two human monoclonal antibodies, directed against the type a and type b flagellar proteins of Pseudomonas aeruginosa, inhibited bacterial motility in vitro specifically and in a concentration-dependent manner. In order to determine if this decreased bacterial motility was associated with a decreased pathogenicity, the ability of these human antiflagellar monoclonal antibodies to attenuate P. aeruginosa-induced pneumonia in the rat was assessed. Incubation of P. aeruginosa with a 1:1 mixture of the human antiflagellar monoclonal antibodies prior to pulmonary instillation significantly (P < 0.05) ameliorated the bacterium-induced decrease in arterial blood oxygen pressure, blunted the increase in respiratory rate, and markedly reduced the area of pulmonary inflammation. Similarly, intravenous administration of the human antiflagellar monoclonal antibodies 1 h after pulmonary instillation of the bacteria also reduced the in vivo pathogenicity of P. aeruginosa. Therefore, human antiflagellar monoclonal antibodies can decrease the in vitro motility of P. aeruginosa and can reduce its in vivo pathogenicity when administered either before or after bacterial challenge.
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